IL-1 Modulator

N-Acetyl-D-Glucosamine (N-Acetyl-2-amino-2-deoxy-D-glucose), the D isomer of N-acetylglucosamine, is an orally active monosaccharide derivative of glucose with anti-tumor and anti-inflammation properties. N-Acetyl-D-Glucosamine is also a bacterial metabolite, which is found in Escherichia coli. N-Acetyl-D-Glucosamine can induce yeast-mycelial conversion in Candida albicans. N-Acetyl-D-Glucosamine also enhances healing of cartilaginous injuries in rabbits.

ADP-β-S (Adenosine 5'-(β-thiodiphosphate)) trilithium is a non-hydrolyzable ADP analog and a P2Y12 receptor agonist. ADP-β-S trilithium activates the P2Y12 receptor in microglia, thereby triggering downstream inflammatory signaling pathways. ADP-β-S trilithium activates P2Y purinergic receptors in rat pancreatic β cells and enhances glucose-induced insulin secretion. ADP-β-S trilithium can be used in the research of diseases such as inflammation and diabetes.

Gamma-glutamylcysteine TFA (γ-Glu-Cys TFA) is an orally active, blood-brain barrier permeable dipeptide. Gamma-glutamylcysteine TFA activates AMPK, SIRT1, IL-4/STAT6, AC/cAMP/PI3K, IGF-1R/IRS1/PI3K, and Nrf2 signaling pathways; it inhibits NF-κB, JAK1/STAT1/3, MAPKs, cadmium-induced p38 MAPK, JNK, and PI3K/Akt signaling pathways. Gamma-glutamylcysteine TFA regulates macrophage polarization, modulates the trafficking of CD36 and GLUT4, induces glutathione synthesis, improves metabolic dysfunction, reduces lipid deposition, ameliorates glucose homeostasis, inhibits apoptosis (Apoptosis), stabilizes mitochondria, suppresses lipid peroxidation, iron accumulation and ferroptosis (Ferroptosis), reduces ds-HMGB1 levels, reverses mechanical hyperalgesia, and alleviates hepatic lipid droplet formation. Gamma-glutamylcysteine TFA is applicable to research related to inflammatory bowel disease, type 2 diabetes, cadmium-induced neurotoxicity, Alzheimer's disease, cerebral ischemia/reperfusion injury, neuropathy, and alcoholic liver disease.

Broussonin E is a phenolic compound and shows anti-inflammatory activity. Broussonin E can suppress inflammation by modulating macrophages activation statevia inhibiting the ERK and p38 MAPK and enhancing JAK2-STAT3 signaling pathway. Broussonin E can be used for the research of inflammation-related diseases such as atherosclerosis.

Kaempferol 3-O-β-D-glucuronide (Kaempferol-3-glucuronide) is a metabolite of kaempferol that can be taken orally and has anti-inflammatory properties. Kaempferol 3-O-β-D-glucuronide can activate AKT/GSK3β phosphorylation and improve glucose metabolism.

Mergetpa is a reversible Arg-carboxypeptidase inhibitor with high affinity. Mergetpa reduces B1R. Mergetpa blocks the overexpression of IL-1β protein and mRNA in glucose-fed rats. Mergetpa significantly increases the expression of IL-1β protein in the renal cortex. Mergetpa is used to block the conversion of kinins and B2 receptor antagonists into metabolites lacking the C-terminal arginine. Mergetpa inhibits the time-dependent enhancement of the response of isolated rabbit aorta to bradykinin. Mergetpa preserves the chemotactic activity of full-length SDF-1α on cells. Mergetpa reverses hyperglycemia, excessive weight gain, elevated levels of oxidative stress markers and overexpression of inflammatory markers in glucose-fed rats.

LRH-1 agonist-2 (Compound 6N) is a selective, full LRH-1 agonist with an EC₅₀ of 15.7 nM. LRH-1 agonist-2 directly interacts with the Thr352 and His390 residues in the LRH-1 binding pocket, promotes allosteric signaling to the activation function surface (AFS), stabilizes the AFS and enhances coactivator recruitment. LRH-1 agonist-2 induces the anti-inflammatory cytokine IL-10, and reduces the pro-inflammatory cytokines IL-1β and TNFα. LRH-1 modulator-1 exerts anti-inflammatory effects in intestinal organoids. LRH-1 modulator-1 can be used in studies related to inflammatory bowel disease.

γ-Hexalactone (γ-Caprolactone) is a gamma-lactone found in ripe fruits. γ-Hexalactone induces DNA damage in human lymphocytes and HepG2 cells, modulates cytokine secretion in human lymphocytes, and reduces recombinant PON1 activity. γ-Hexalactone serves as a dose-dependent oviposition inhibitor against Bactrocera oleae. γ-Hexalactone can be used for the research of Bactrocera oleae pest management.

JTE-907 is a selective and orally active cannabinoid CB2 receptor inverse agonist and exerts anti-inflammatory effects. JTE-907 upregulates IL-6, MCP-1, IL-1β, VEGF, ANGPTL4, and TRPV1 in mature adipocytes. JTE-907 downregulates CB1, MCP-1, and IL-1β in preadipocytes. JTE-907 inhibits ear swelling in mice. JTE-907 reverses the protective effects of CB2 agonists and Anandamide (HY-10863) against cytokine-evoked colonic mucosal damage. JTE-907 can be used for the research of allergic dermatitis, obesity, and colitis.

Hidrosmin, a flavonoid, is derived from Diosmin (HY-N0178). hidrosmin exerts a beneficial effect against diabetic nephropathy (DN) by reducing inflammation, oxidative stress, and senescence pathways. Hidrosmin can be used for the research of venous insufficiency and diabetes mellitus.

Chitoheptaose is an orally active chitooligosaccharide (degree of polymerization = 7). Chitoheptaose can be extracted from the exoskeletons of crustaceans, such as the shells of crabs, shrimps and lobsters. Chitoheptaose reduces pro-inflammatory cytokines while increasing the levels of anti-inflammatory cytokines (decreasing the levels of pro-inflammatory cytokines IL-1β, IL-17A and IFN-γ, and increasing the level of the anti-inflammatory cytokine IL-10). Chitoheptaose possesses antioxidant, anti-inflammatory and anti-Apoptotic activities. Chitoheptaose improves cardiac parameters, alleviates myocarditis injury, and exerts cardioprotective effects in a rat model of myocarditis. Chitoheptaose can be used in studies related to myocarditis.

DLX2323 is an interleukin-1β (IL-1β) modulator. DLX2323 is promising for research of inflammatory diseases.

MR-39 is a FPR2 agonist (EC₅₀ = 3.9 μM). MR-39 activates FPR2 to promote neuroinflammation resolution (downregulates IL-1β and TNF-α, modulates NF-κB), upregulates synaptic proteins (synaptic proteins) and improves dendritic spine morphology. MR-39 inhibits MAPK/ERK and AKT phosphorylation in glioblastoma, induces S-phase arrest, and suppresses migration, angiogenesis, and hypoxic adaptation. MR-39 reduces Aβ plaque burden via inhibiting MyD88/NF-κB and NLRP3 inflammasome. MR-39 can be used for research on autism spectrum disorder, Alzheimer's disease, and glioblastoma.

APH003 is an orally active IRAK4 PROTAC degrader with a DC₅₀ of 0.74 nM in human peripheral blood mononuclear cells (hPBMCs). APH003 recruits IRAK4 to CRBN to form a ternary complex, mediates the ubiquitination and degradation of IRAK4 via the ubiquitin-proteasome pathway, and inhibits the kinase activity of IRAK4. APH003 inhibits LPS- or IL-1β/LPS-induced phosphorylation of ERK, JNK and NF-κB. APH003 inhibits the secretion of TNF-α, IL-6, IL-8 and IL-13 by stimulated hPBMCs. APH003 exhibits anti-inflammatory activity in rat TNBS-induced intestinal inflammation models and mouse IL-33-induced skin inflammation models. APH003 can be used in research related to inflammatory bowel disease and skin inflammation.

Antiflammin-1 is an anti-inflammatory peptide 1 (MQMKKVLDS). Antiflammin-1 is a derivative of uteroglobin. Antiflammin-1 has anti-inflammatory and antifibrotic actions in bleomycin (HY-108345)-induced lung injury.

2-ARA-LysoPtdEtn (1-Lyso-2-arachidonoyl-sn-glycero-3-phosphoethanolamine) is an orally active polyunsaturated acyl lysophosphatidylethanolamine. 2-ARA-LysoPtdEtn diminishes formation of LTC₄, LTB₄, and 12-HETE. 2-ARA-LysoPtdEtn lowers levels of IL-1β, IL-6, TNF-α, and NO. 2-ARA-LysoPtdEtn augments IL-10 levels and upgrades formation of 15-HETE and LXA₄. 2-ARA-LysoPtdEtn can be used for the research of peritonitis.

Lemairamin (Wgx-50) is a hydroxylamine compound. Lemairamin can be isolated from the pericarps of the Zanthoxylum plants. Lemairamin activates α7nAChR, stimulates the expression of IL-10 and POMC. Lemairamin shows a decrease in Akt. Lemairamin attenuates DSS-induced intestinal inflammation. Lemairamin alleviates pain hypersensitivity.

13 (S)-HOTrE is an oxylipin metabolite of α-Linolenic acid (HY-N0728). 13 (S)-HOTrE mediates the inactivation of the NLRP3 inflammasome through the PPAR-γ pathway to exert anti-inflammatory effects. 13 (S)-HOTrE inhibits NF-κB nuclear translocation, ROS production, autophagy and IL-1β levels, induces apoptosis, and increases IL-10 levels. 13 (S)-HOTrE alleviates LPS-induced inflammatory responses in macrophages, prolongs the survival time of septic mice, and regulates the immunometabolic phenotype in parenteral nutrition mouse models. 13 (S)-HOTrE can be used in the research of immune and inflammation-related diseases.

Chitohexaose hexahydrochloride is a small molecular polysaccharide. Chitohexaose hexahydrochloride inhibits the binding of AgW to TLR4. Chitohexaose hexahydrochloride upregulates IL-10, inhibits LPS-induced upregulation of ROS, induces alternative activation of macrophages/monocytes, and suppresses LPS-induced production of TNF-α, IL-1β and IL-6. Chitohexaose hexahydrochloride reverses the mortality of mice challenged with APAP or LPS. Chitohexaose hexahydrochloride can be used in research related to Acetaminophen (HY-66005)-induced hepatotoxicity and endotoxemia.